In today's animal production systems there is a delicate balance between intestinal flora and its host, and disruption of this balance (by e.g. bacterial infection) has a negative impact on the overall efficiency of the animals (Eckel, 1999). Knowledge of the problems of intestinal microbial infection in animals opens the door to radically new ways of bio-regulatory processes to be influenced by nutrition concepts, the frequency reduction of diarrhoea and even mortality, by stabilizing the intestinal flora. In the past, these infection problems were partially solved by adding antibiotics to the feeds as growth stimulator.
Currently, decades after the discovery of traditional antimicrobials (e.g. penicillin), many bacteria became resistant to one, and in many cases multiple antimicrobials (Guillot, 1989). This resistance appears fatal for thousands of people each year and results in high medical and economic costs (Barton, 1998). The problem of immunity to antimicrobial agents is ubiquitous, and is partly caused by the worldwide use of antimicrobials in animal nutrition, since its addition to food formulations results in a higher efficiency (reduced feed conversion and faster growth) (Dupont & Steele, 1987) and because the use of more than half of all antimicrobial agents is associated with animal production (Aarestrup, 1999). In some countries, e.g. in the European Community, this has already led to a general prohibition of all antimicrobials used as growth enhancers in food formulations (Muirhead, 1998).
The problem with most traditional antimicrobials and other growth promoters used today is that they attack bacteria on an intracellular level (Guillot, 1989). In particular, they inhibit key enzymes involved in the synthesis of cellular building blocks. In this approach, bacteria can develop mutations in the enzymes involved or they can develop mechanisms to pump quickly the antimicrobial agents out of the cell. Alternatively they can develop enzymes that directly degrade the antimicrobial agent (e.g. β-lactamase) (Neu et al., 1980). By plasmid transfer (via microbial conjugation), resistance can be transferred quickly from one to another microbial cell (expansion of resistance) (Finland, 1971).
Since the global negative response to the use of traditional antimicrobials as growth promoters in animal nutrition, research is conducted in order to develop new types of (natural) antimicrobials or growth promoters (especially those based on an alternative method) (Mazza, 1998). The search for alternative (natural) antimicrobials is now mainly focused on the use of several (organic) acids (Eckel, 1997), new active probiotics (Chiquet & Banc Hair, 1998), prebiotics (Olsen, 1996), enzymes (Hruby & Cowieson, 2006), some plants (onion and garlic) and herb extracts (essential oils) (De Koning & Hongbiao, 1999).
Today, different types of oligosaccharides are used in various applications. WO2006/022542 describes the combined use of indigestible oligosaccharides and digestible galactose saccharides for the treatment and/or prevention of respiratory infections. WO2004/074496 describes the use of oligosaccharides consisting of galactose and glucose to develop beneficial bacteria in the gastrointestinal tract of animals. JP2002226496 describes oligosaccharides obtained by hydrolyzation of polysaccharides such as fucoidan with an anti-infective activity against E. coli and Vibrio. CN1370784 describes chitinamine oligosaccharide, which potentially can be used in cancer therapy and in the treatment of hepatosis, improving the function of the intestinal tract and in the treatment and prevention of senility. JP2002121138 describes the use of oligosaccharides from chicken egg yolks, especially sialyl-oligosaccharides, oligosaccharide-bound proteins and oligosaccharide peptides to protect the gastrointestinal tract from infection. U.S. Pat. No. 6,069,137 describes the treatment of travel diarrhoea caused by enterotoxinogenic E. coli by administration of oligosaccharides, containing β-galactose, covalently bonded to silica particles by a linker whereby said particles are secreted from the gastrointestinal tract. EP1018342 describes the treatment of SLT-mediated enteric infections using a solid inert affinity carrier that can be excreted from the gastrointestinal tract, on which a disaccharide is covalently bound, having affinity with SLT. U.S. Pat. No. 5,939,397 describes a method for treating cholera by administration of a 1-3 oligosaccharide, with affinity for one or more V. cholerae serotypes, covalently bonded through a linker to a solid, inert carrier.
Various types of MCFAs are also used in several applications. In this context, EP1294371 describes specific MCFAs as inhibitors of microbial and especially bacterial and fungal contamination and growth. In particular, EP1294371 describes the use of essential equal amounts of caprylic acid (C8) and capric acid (CIO) as antimicrobial agents, mainly active in an acidic environment like the stomach.
The aim of the present invention is to develop a feed supplement with enhanced effects on the microbial ecosystem. In particular, the present invention wants to increase the specificity and activity of feed supplements and a faster operation thereof, to improve the enteric microbial ecosystem. This invention introduces a specific combination of growth promoters which have a synergistic beneficial effect on the efficiency of animal production, feed conversion, nutrition, health and wellbeing of individuals. In this regard, the combined use of tri- and/or tetra-oligosaccharides with MCFAs can be considered as a new and innovative agent with growth stimulating properties.